Angiogenesis refers to the phenomenon of formation of new blood vessels from pre-existing veinlets or capillary blood vessels in animal tissues or organs by migration, proliferation and lumen formation of vascular endothelial cells. The phenomenon is not only caused in the morphogenetic stages or growth stages of animals, but also caused along with the curing of damages of tissues, restoration processes of inflammations, and menstrual periods, which are controlled both by promoting factors and inhibiting factors of angiogenesis. Therefore, it is important to maintain a balance between the promoting factor and the inhibiting factor in order to maintain homeostasis of the blood vessels.
However, in tumor tissues, angiogenesis is enhanced by overexpression of the angiogenesis promoting factor, which consequently leads to a further augmentation of the tumor tissues. Therefore, as the anticancer therapy, a method of administering an angiogenesis inhibiting factor or an inhibitor for an angiogenesis promoting factor or the like has been considered.
Vasohibins are polypeptides found by the present inventors, to which Vasohibin-1 and Vasohibin-2 belong as homologues. These Vasohibins have been known to be expressed in the vascular endothelial cells by stimulations of angiogenesis promoting factors (VEGF, FGF-2 or the like) secreted from tumor cells, interstitial cells, macrophages, and the like, and act on the endothelial cells themselves in an antocrine manner, to have an action of inhibiting angiogenesis (see, Patent Publications 1 and 2).
On the other hand, the present inventors have also found that Vasohibin-2, i.e. AK022567 protein, and BC051856 protein, BC053836 protein, BC028194 protein, and AY834202 protein, which are splicing variants thereof, which are disclosed in Patent Publication 2, have actions of promoting angiogenesis in the same hypoxia state as pathologies such as cancer and cerebrovascular disorders, and reported (see, Patent Publication 3).